Background

Xanthenes are a special class of oxygen-incorporating tricyclic compounds. Structurally related to xanthones, the presence of different substituents in position 9 strongly influences their physical and chemical properties, as well as their biological applications.

This review explores the synthetic methodologies developed to obtain 9H-xanthene, 9-hydroxyxanthene and xanthene-9-carboxylic acid, as well as respective derivatives, from simple starting materials or through modification of related structures. Azaxanthenes, bioisosteres of xanthenes, are also explored. Efficiency, safety, ecological impact and applicability of the described synthetic methodologies are discussed. Synthesis of multi-functionalized derivatives with drug-likeness properties are also reported and their activities explored.

Synthetic methodologies for obtaining (aza)xanthenes from simple building blocks are available, and electrochemical and/or metal free procedures recently developed arise as greener and efficient methodologies. Nonetheless, the synthesis of xanthenes through the modification of the carbonyl in position 9 of xanthones represents the most straightforward procedure to easily obtain a variety of (aza)xanthenes. (Aza)xanthene derivatives displayed biological activity as neuroprotector, antitumor, antimicrobial, among others, proving the versatility of this nucleus for different biological applications. However, in some cases their chemical structures suggest a lack of pharmacokinetic properties being associated with safety concerns, which should be overcome if intended for clinical evaluation.

中文翻译：

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药物化学中的黄嘌呤–合成策略和生物活性

背景

黄嘌呤类是一类特殊的掺氧三环化合物。在结构上与氧杂蒽有关，位置9上不同取代基的存在强烈影响其物理和化学性质以及它们的生物学应用。

这篇综述探讨了从简单的起始原料或通过相关结构的修饰获得9 H -an吨，9-羟基x吨和and吨-9-羧酸及其衍生物的合成方法。还研究了黄嘌呤，黄嘌呤的生物等排体。讨论了所述合成方法的效率，安全性，生态影响和适用性。还报道了具有药物样性质的多功能衍生物的合成，并探讨了它们的活性。

从简单的结构单元获得（氮杂）黄嘌呤的合成方法是可用的，并且最近开发的电化学和/或无金属方法是更绿色和有效的方法。然而，通过修饰黄嘌呤的9位上的羰基合成黄嘌呤代表了最容易获得各种（氮杂）黄嘌呤的最直接的方法。（氮杂）黄嘌呤衍生物显示出作为神经保护剂，抗肿瘤剂，抗微生物剂等的生物学活性，证明了该核对于多种生物学应用的多功能性。但是，在某些情况下，它们的化学结构表明缺乏与安全性相关的药代动力学特性，如果打算用于临床评估，则应予以克服。